Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: A multimodal evoked potentials study

Migraine accounts for the highest headache-related disability of the primary headaches. Despite the great knowledge achieved on the pathophysiology of migraine, commonly available preventive treatments are effective in only about half of patients. Many have disabling and uncomfortable adverse effects. Pharmacological and non-pharmacological treatments that are more effective are very welcome [1, 2, 3]. In recent decades, specific dietetic interventions raised the interest of experts in the field of headaches. The evidence for an association between migraine, obesity [4, 5], and metabolic syndromes such as insulin resistance [6, 7] has supported this approach because they could be improved via specific dietary patterns. We reported a case of a pair of overweighed twin sisters whose high-frequency migraine improved during a ketogenic diet (KD) that they followed to lose weight [8]. Their KD consists of a very low-calorie ketogenic diet (VLCKD) including a drastic restriction in carbohydrate and lipid intake that promotes fat metabolism and ketone body synthesis. After our initial accidental observation, we proved the clinical efficacy of VLCKD in a population of overweighed migraine patients. This was not related to diet-induced weight loss because the same improvement was not observed during a standard dietetic regimen [9]. According to the experimental observations in animal models, the underlying mechanisms of KD efficacy could be related to its ability to modulate cortical excitability [10, 11]. Time-locked cortical potentials evoked by a sensorial stimulation have been used frequently as a model to study migraine brain excitability. With these methods of clinical neurophysiology, researchers frequently observed a lack of cortical response habituation during any kind of stimulus repetition including visual and somatosensory [12, 13]. Habituation is a form of plastic learning and is a protective mechanism intended to limit cortical excitability. It prevents neuronal stress and excessive accumulation of metabolites such as lactate [14]. Here, in order to investigate if KD may exert its prophylactic effect regulating abnormal cortical information processing and excitability, we evaluated for the first time the influence of 1-month KD on habituation of visual and somatosensory cortical evoked potentials in a group of episodic migraineurs during the interictal phase.